It has been suspected by some that acetylcholine, the normal neurotransmitter substance at the nerve terminals of somatic nerves, pre-ganglionic autonomic nerves and post-ganglionic parasympathetic nerves, might have an extraneuronal function in the regulation of spontaneous myocardial rhythm. Therefore, non-neuronal autonomic mechanisms, arrthythmias and certain antiarrhythmics will be investigated using cultured embryonic chick heart cells. The objective of the study is to elucidate basic cholinergic and adrenergic physiological mechanisms and to evaluate their role in the control of cardiac rhythmicity, arrhythmogenesis and antiarrhythmic drug action. Experimental results will be obtained by studying neuro-hormonal, ionic and other drug induced changes in the spontaneous contractile rate of cultured cells under normal and arrhythmic conditions. Histochemical and biochemical procedures will be utilized to determine and characterize myocardial cell active transport processes, endogenous hormonal substances, their biogenesis, metabolism, localization and cellular storage. Specifically, the proposed work tests two hypotheses, (a) that endogenous intracellular non-neuronal acetylcholine acts as a "local hormone" in the control of cardiac rhythmicity and (b), that the extra- neuronal uptake of catecholamines, at sites additional to the beta- adrenergic receptor, may serve to regulate the myocardial stimulatory properties of these agents (eg:-Cardiac sensitization to catecholamines in catecholamine-hydrocarbon induced arrhythmias).